The Effect of Kaempferol on Autophagy and Nrf-2 Signaling in a Rat Model of Aβ1-42-induced Alzheimer’s Disease

Abstract

Background: Numerous pieces of evidence support that oxidative stress is a key factor inthe pathogenesis of neurodegenerative diseases, like Alzheimer’s Disease (AD). Suppressionof oxidative stress is an attractive strategy and flavonoids as potent natural antioxidants areextremely noticeable.Objectives: In this study, the effects of Kaempferol (KMP) were evaluated on passive avoidancememory, hippocampal Nrf-2, and beclin-1 expression in a rat model of Aβ1-42 –induced AD.Materials & Methods: Forty male Wistar rats weighing 200-250 g were divided into fivegroups (n=8); sham-operated, AD model, and KMP treatment (5, 7.5, 10 mg/kg, i.p. for threeweeks). Animals received an intracerebroventricular injection of amyloid-beta (1-42) toestablish an AD model. Passive avoidance memory of rats was evaluated using a shuttle boxon day 21; Step-Through Latency (STL) and time spent in The Dark Compartment (TDC)were recorded. Then, hippocampus homogenates were used for biochemical and molecularanalysis by real-time PCR, western blot, and ELISA.Results: It was found that KMP improved memory evidenced by increased STL (P≤0.05)and decreased TDC (p≤0.01). KMP also increased the levels of Total Antioxidant Capacity(TAC) in the hippocampus of rats (P≤0.05). In addition, KMP enhanced the expression of Nrf-2 mRNA (P≤0.001) and beclin-1 protein in the hippocampus tissues (P≤0.001).Conclusion: Overall, it is suggested that the memory-improving effect of KMP is mediated,at least in part, by enhancing Nrf-2 and TAC. KMP is also able to induce autophagy throughthe expression of beclin-1.